Methods for dividing a racemate into optical isomers (optical resolution methods) include a method of using an enzyme, a method of reacting optical isomers for conversion into salts and dividing the salts, a method of preparing a diastereomer mixture by reactions with optical isomers and then purifying the mixture for separation, and the like. Among them, the method of using an enzyme does not require optical isomers, and accordingly the method is advantageous since the reaction can be performed at low cost, for example. However, said method also has a problem that it is generally difficult to regioselectively and stereoselectively hydrolyze a specific alkoxycarbonyl of a triester or the like having two or more alkoxycarbonyls in a single molecule.
As methods for producing an optically active carboxylic acid derivative by regioselective and stereoselective hydrolysis using an esterase, Patent document 1 and Non-patent documents 1 and 2 report methods of asymmetrically hydrolyzing an α-(lower alkyl)-α-(protected amino)malonate diester derivative by using a pig liver esterase to produce an optically active α-(lower alkyl)-α-(protected amino)malonate monoester derivative.
(In the formulas, R4 represents benzyloxycarbonyl, tert-butoxycarbonyl, or the like, and R5 represents a lower alkyl or the like.)
Patent document 2 describes a method for producing (R)-2-amino-2-ethoxycarbonylsuccinimide (henceforth referred to as compound B), which is a key intermediate of the compound A, by using an esterase.
Methods for preparing the compound A from the compound B are described in Patent document 3, Non-patent document 3, and the like, and a method of preparing 4-tert-butyl 1-ethyl 2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinate by reacting diethyl 2-benzyloxycarbonylaminomalonate and tert-butyl 2-bromoacetate is described in Reference Example 1 of Patent document 4.